PLASMA-PROTEIN BINDING OF BASIC DRUGS .1. SELECTIVE DISPLACEMENT FROM ALPHA1-ACID GLYCOPROTEIN BY TRIS(2-BUTOXYETHYL) PHOSPHATE

Abstract

Protein binding of a number of basic drugs was inhibited when blood is collected in Vacutainer tubes. The plasticizer tris(2-butoxyethyl) phosphate (TBEP), present in plasma collected in Vacutainers, was a potent inhibitor of alprenolol and imipramine protein binding. Its concentration in plasma could quantitatively explain the displacement phenomenon. Alprenolol binding to a solution of a physiologic concentration (0.67 g/l, 0.015 mM) of .alpha.1-acid glycoprotein (orosomucoid) was decreased from 76% to 16% by addition of 10 .mu.g/ml (0.026 mM) of TBEP, while imipramine binding was decreased from 69% to 13%. Alprenolol and imipramine binding to albumin and lipoproteins was virtually unchanged by TBEP. Due to its selective effect on binding to .alpha.1-acid glycoprotein, TBEP may be a useful tool for studying plasma protein binding of basic drugs.